Composition and its use as a food supplement or for lowering lipids in serum

ABSTRACT

A composition on basis of soybean ingredients contains (a) isolated soy protein, (b) soybean fibres, and optionally an additional protein source, a carbohydrate source, a fat source, flavouring agents, vitamins, minerals, electrolytes, trace elements and other conventional additives, the amount of (a) being such that the protein content provides at least 15% of the total energy content of the composition, and (I) the weight ratio of (a) to (b) is at least 2 and (a) is at least 75 wt % of the total protein content, or (II) the ratio of (a) to (b) is at least 3. The composition is useful as partial or total diet for overweight or obese subjects and is furthermore useful for lowering the cholesterol level and the triglyceride level and for increasing the HDL/LDL-cholesterol ratio in serum.

This is a continuation of parent application Ser. No. 09/143,120 filedAug. 28, 1998, now U.S. Pat. No. 6,136,367, continuation ofPCT/IB97/00152, filed Feb. 12, 1997.

The present invention relates to a composition on basis of soybeaningredients. More particularly, the invention relates to a nutritionalcomposition which is useful as a weight-reducing diet for overweight orobese subjects. Furthermore. the invention relates to such a nutritionalcomposition, which is useful for lowering serum lipids

Adipositas or obesity and overweight in general is a widespread problemin large parts of the world. At the same time, increased healthconsciousness has stimulated the interest in “keeping the slim line”. Alarge number of different diets have therefore been put on the marketaiming at a rapid weight reduction.

Some of these diets must be considered unwarrantable seen from anutritional point of view as they are based on a very unbalanced intakeof nutrients which very quickly will result in deficiency of essentialnutrients.

Other diets are based on nutritional preparations being composed in sucha way that, at a low calorie content, they supply the necessaryproteins, vitamins and minerals. Some of these preparations are in theform of powders containing sources of protein, carbohydrate and fat, andoptionally flavouring agents, preservatives, vitamins, minerals andother conventional additives. Before intake, the powders are stirred upin water and then taken as a drink or a gruel. However, the knownpreparations suffer from a number of deficiencies. Many known powderscan only with difficulty be stirred up in water so that the stirred uppreparations will have a lumpy and gritty consistency which makes themvery unpleasant to take. At the same time, sedimentation occurs veryquickly, involving the risk that essential components such as sparinglysoluble minerals are not taken in, but remain as a sediment at thebottom of the glass. Finally the preparations have an unpleasant tangwhich persists as an after-taste a long time after the preparation hasbeen taken. These disadvantages have the effect that many persons breakoff the diet too soon.

EP0 425 423 B1 discloses a process for the preparation of a powdery,low-calorie nutritional preparation, especially for use as the main orsole nutrition in the treatment of adipositas. The preparation has abalanced composition of sources of protein, carbohydrate and fat, andoptionally contains flavouring agents, preservatives, vitamins, mineralsand other conventional additives. The protein source is a combination ofa soy protein concentrate and skirmed milk powder. The soy proteinconcentrate is a product prepared from shelled soybeans by removing mostof the oil and water soluble, non-protein constituents. Soy proteinconcentrate typically contains 66.0% protein, 17.0% carbohydrate, 6.0%water, 5.6% ashes, 4.0% wood substance, and 1.4% fat. The carbohydratecontent is typically present as fibres which are insoluble in water. Atypical soy protein concentrate does not contain all the essential aminoacids in sufficient amounts. In particular, histidine and tryptophan arelimitating amino acids in soy protein concentrate. In order to supplyall the essential amino acids, the known nutritional preparation alsocontains skimmed milk powder as a protein source. However, skimmed milkis not a desirable protein source in certain parts of the world, inparticular Southern Europe, Asia and Africa where lactose intolerance isnot unusual due to lack of the lactose-degrading enzyme, lactase.Overweight and obesity are often accompanied by an increased fattycontent in the blood, and for altering the lipid profile EP-0 425 423 B1suggests supply of separate capsules comprising fish oil containingpolyunsaturated fatty acids along with the nutritional preparation. Itwould be desirable if the intake of separate fish oil capsules could beavoided for improving the lipid profile. Thus, it would be highlydesirable to provide a nutritional preparation which in itself had abeneficial lowering effect upon the lipid level.

As mentioned above, some of the diets presently on the market for weightreduction are based on an unbalanced intake of nutrients, which mayresult in deficiency of essential nutrients. In particular, a sufficientintake of protein supplying all the essential amino acids is veryimportant in connection with any weight reducing treatment. Typically,22-36% of the overweight is lean body mass (LBM), which is the fat-freebody mass, such as musculature. The loss of proteins from e.g. musclesresults in elimination of nitrogen from the body, which can be measuredindirectly by determination of the concentration of uric acid in serum.If the concentration of uric acid increases substantially during aweight reduction, the reason may be too much degradation of musculature.

In New England Journal of Medicine, Vol. 333, Aug. 3, 1995, ameta-analysis of the effects of soy protein intake on serum lipids, hasbeen described. In this study, the authors examined the relation betweensoy protein consumption and serum lipid concentrations in humans. It wasfound that ingestion of diets containing soy protein, as compared withcontrol diets was accompanied by significant reduction in serumconcentrations of total cholesterol, LDL-cholesterol and triglycerides.Soy protein intake did not significantly affect serum HDL cholesterolconcentrations. The effect of soy protein intake was dependent uponinitial cholesterol concentration. Subjects with normal cholesterollevels had non-significant reductions of 3.3%, and also subjects withmild hypercholesterolemia had non-significant reductions of 4.4%. Onlysubjects with moderate and severe hypercholesterolemia had significantdecreases in cholesterol levels of 7.4% and 19.6%, respectively. Thepattern of changes in serum LDL-cholesterol concentrations was similarto the pattern for total cholesterol concentrations. Also changes inserum triglyceride concentrations were significantly related to theinitial serum triglyceride concentrations. Various types of soy proteinwere studied, such as isolated soy protein, textured soy protein, or acombination, and it was found that the type of soy protein did not haveany significant effect on the net change in serum cholesterolconcentrations. The study did not consider a simultaneous intake of thevarious types of soy proteins along with soy fibres. This meta-analysisof the effects of soy protein intake on serum lipids found its way tothe international press as a sensational finding that soy protein iseffective in lowering serum cholesterol, and articles appeared inInternational Herald Tribune on Aug. 4, 1995, Chicago Tribune on Aug. 3,1995, and in New York Times on Aug. 3, 1995.

Potter et al., Am J Nutr Clin 1993; 58; 501-6, studied the effects ofsoy protein consumption with and without soy fiber-on plasma lipids inmildly hyperchoesterolemic men. Dietary treatment included 50 g proteinand 20 g dietary, fiber from soy flour, isolated soy protein/soycotyledon fiber, isolated soy protein/cellulose, and non-fat drymilk/cellulose in conjunction with a low-fat, low-cholesterol diet. Theprotein and dietary fibres were prepared as baked products andsubstituted into the diet. In the experiment using isolated soy proteinand soy cotyledon fiber the subjects received per day 50 g isolated soyprotein, 50 g other proteins, including 36 g animal and 14 g vegetableprotein, carbohydrates corresponding to 55% energy intake, 20 g soycotyledon fiber, fat corresponding to <30% of total energy content, and200 mg cholesterol. As a result of the study, it was found that totaland LDL-cholesterol concentrations can be lowered significantly inmildly hypercholesterolemic men, which was attributed to the replacementof 50% of dietary protein with soy protein. Similar depressions in bloodlipids were noted for isolated soy protein, whether it was consumed inconjunction with soy cotyledon fiber or cellulose fiber. Plasmatriclycerides concentrations were unaffected by the various dietarytreatments described in the article. The study did not reveal anyadditive cholesterol-lowering effect of concurrent intake of cotyledonsoy fiber with isolated soy protein, and specifically the authorsstated: “Whether or not there is an added benefit in lowering bloodcholesterol concentrations from increased concurrent intake of soyprotein and fiber in humans is not known.”

Bakhit et al., J Nutr (in press) 1993, also studied mildlyhypercholesterolemic men receiving a baseline diet in combination withfour experimental treatments. For each dietary treatment, four types ofmuffins were prepared and baked, individually packaged, frozen andstored at −20° C. until distributed to subjects on a weekly basis. Thefour muffins containing appropriate test proteins and fibres were addedto the basal diet replacing a total of 2.51 MJ of the subject's normalintake. The test proteins used were isolated soy protein and casein assodium casenite. Fibres were soy cotyledon fibres and cellulose fibres.Protein and fiber were incorporated into the muffins to provide 25 g ofprotein and 20 g of dietary fiber daily in four muffins. The weightratio between protein and fibres were in all cases 1.25, and the amountof protein corresponded to 20% of the total energy content. The coal ofthe study was to evaluate the ability of a relatively low level ofsoybean protein intake (25 g≈5% of energy intake per day) with andwithout soy cotyledon fibres, to decrease plasma lipid concentrationswhen consumed along with a typical low-lipid diet. As a result, it wasfound that addling of 25 g of soybean protein to a low-fat,low-cholesterol diet lowers total cholesterol concentrations in men withelevated blood lipids. In subjects having lower blood cholesterolconcentrations (<5.7-mmol/l), this level of soybean protein intake didnot influence blood lipids, and it was suggested that plasma lipids mayeven be elevated in some subjects following soybean ingestion. Alsoother previous studies have found that in general individuals withpre-existing hypercholesterolemia respond to soybean protein, whereasindividuals with normal cholesterol values do not. Bakhit et al. did notobserve an additive effect of concurrent ingestion of soybean proteinand soybean fiber. According to the authors, soybean protein may affectcholesterol metabolism directly, possible via modulation of endocrinestatus, whereas soybean fiber most likely acts by interruptingenterohepatic circulation of bile.

In conclusion, the above-discussed studies of Potter et al. and Bakhitet al. did not find any serum lipid lowering effect in subjects having anormal blood cholesterol concentration below 5.7 mmol/l.

High serum levels of cholesterol cause disease and death by contributingto the formation of atherosclerotic plaques in arteries throughout thebody. In order to reduce high serum cholesterol levels, subjects may beput on a low fat, low cholesterol diet or may be treated withmedicaments such as statins, or a combination of both. The statinsselectively inhibit HMG-CoA-reductase which is the controlling enzyme inthe cholesterol synthesis. The enzyme increases the formation of LDLreceptors and among other hereby decreases the level of LDL-cholesterolin the blood. Once the serum level of cholesterol has been lowered to anormal value, it will be desirable to avoid further medication bysubjecting the individual to a diet which can retain serum levels ofcholesterol at a normal value and more preferably lower the serumcholesterol concentration below a value of 5.7 mmol/l. Also manyphysicians find that a serum cholesterol level of 5.7 mmol/l is toohigh, especially in subjects with a history of cardiovascular disease,where it is medically proven that a lower cholesterol level than 5.7mmol/l reduces myocardial infarction and deaths considerably. Thus,there is a need for a composition which can lower serum cholesterolconcentrations in subjects having a normal serum lipid concentration.

It has now surprisingly been found that serum lipid concentrations insubjects having normal serum lipid concentrations are significantlylowered by intake of a composition according to the present invention onbasis of a particular combination of soy bean ingredients. As a furtherbenefit, the composition of the present invention not only lowers normalserum lipid concentrations, but it also has a lipid-lowering effect insubjects having increased serum lipid concentrations. The lipid-loweringeffect is more-pronounced the higher the initial value. It has also beenfound that the composition of the invention can lower the level ofcholesterol and triglycerides in subjects who have been treated withcholesterol lowering medications such as statins. Furthermore, it hasbeen found that a composition of the present invention can lower theserum cholesterol level in a hypercholesterolemic patient whosecholesterol level has been partly lowered by a diet with a low fat andcalorie intake, recommended by doctors.

A composition according to the present invention has been found toreduce the level of total cholesterol and total triglycerides. TheHDL/LDL-cholesterol ratio in serum is also improved. Also, it has beenfound that the lipid-reducing activity of such a composition can beincreased by adding increasing amounts of isolated soy protein,carbohydrate and fat to the composition. It is particularly surprisingthat increasing amounts of fat may lower serum lipid concentrations asit is well known that the amount of fat in food is considered to beresponsible for increased cholesterol and triglyceride levels. As afurther surprising feature it has been found that the increase in uricacid concentration is lowered when the compositions are used as a totaldiet. Therefore, a nutritional composition in accordance with thepresent invention is very useful as a nutritional composition in aweight reduction treatment for overweight or obese subjects, who veryoften have increased levels of triglycerides and are at risk of havinghypercholesterolemia. Furthermore, a nutritional composition inaccordance with the present invention will be useful as a nutraceutical,i.e. a nutritional composition used as a pharmaceutical. In this aspect,the composition is a medicament based upon naturally occurring rawmaterials for lowering the blood cholesterol and triglyceride levels andfor increasing the HDL/LDL-cholesterol ratio in serum.

In a first aspect of the present invention, there is provided anutritional composition on basis of soybean ingredients comprising

(a) isolated soy protein

(b) soybean fibres, and

optionally an additional protein source, a carbohydrate source, a fatsource, flavouring agents, vitamins, minerals, electrolytes, traceelements and other conventional additives,

the amount of (a) being such that the protein content provides at least15% of the total energy content of the composition, and the weight ratiobetween (a) and (b) being at least 2. Preferably, the weight ratiobetween (a) and (b) is at least 2.5 and more preferably the ratio is atleast 3 with the most preferred value being between 3 and 4.

Isolated soy protein is the major proteinatious fraction of soybeans. Itis prepared from high quality, sound, cleaned, dehulled soybeans byremoving a preponderance of the non-protein components which shallcontain not less than 90% protein (N×6.25) on a moisture free basis. Thepreparation takes place through a series of steps in which the soybeanprotein portion is separated from the rest of the soybean. The removalof carbohydrate results in a product which is essentially bland inflavour and therefore useful in a nutritional composition for humans.The isolated soy protein used in the composition of the presentinvention should preferably supply all the essential amino acids in theamounts required for humans. Preferably, the isolated soy protein shouldmeet or exceed the essential amino acid requirement pattern for childrenand adults as established by the Food and Agricultural Organisation,World Health Organisation and United Nations University (FAO/WHO,UNU).Also the preferred isolated soy protein should be highly digestible,comparable in digestibility to milk, meat, fish and egg protein.Finally, the preferred isolated soy protein shall be effective inmaintaining nitrogen balance when consumed at the recommended proteinintake level. Preferred isolated soy protein products which meet theforegoing requirements are supplied by Protein TechnologiesInternational under the brand name SUPRO®. SUPRO® isolated soy proteinsare supplied in many different qualities. One particularly preferredproduct is SUPRO PLUS® 2100, which is a protein product consisting ofisolated soy protein, sweet diary whey and calcium phosphate. It offersexcellent nutritional properties, a bland flavour and smooth mouthfeel.It is spray-dried to provide excellent dispersibility and suspensionproperties, and it is particularly recommended for dry blended beveragesdesigned to be mixed with water, juice or milk. Another particularlypreferred isolated soy protein product is SUPRO® 661, which is a proteinwhich offers excellent dispersibility, bland flavour and excellentnutritional properties. It has a high bulk density and is thereforerecommended for dry blended applications requiring a high densityprotein source to achieve certain can fill requirements.

Preferably, the isolated soy protein is the main or sole protein sourcein a nutritional composition according to the present invention.However, parts of the protein source may be provided by other proteinssuch as soy protein concentrate, skimmed milk, preferably as a powder,and other vegetable or animal, including diary, proteins. Preferably, atleast 90 weight % of the protein source is isolated soy protein, andless preferred at least 50% of the protein source is isolated soyprotein.

The soybean fibres used in the nutritional composition of the presentinvention are fibres which may be isolated from soybeans in a number ofdifferent ways. One available source would be soy protein concentrate,as discussed above. Preferably, the soybean fibres are isolated from thecotyledon of soybeans. In particular, such fibres are derived fromdehulled and defatted soybean cotyledon and are comprised of a mixtureof cellulosic and non-cellulosic internal cell-wall structuralcomponents. Such fibres are distinctly different from soy fibes derivedfrom soy hulls as well as other fiber sources. Soy cotyledon fibres arebland-tasting, contain no cholesterol and are low in fat and sodium.They have good water-binding properties and low caloric content, whichmake them ideal as bulking agents. Soy cotyledon fibres supplied in afat-modified and low-cholesterol diet have been found to further reduceblood cholesterol level in subjects with elevated plasma cholesterollevels. The effect is a lowering of sternum total cholesterol and alowering of LDL-cholesterol. HDL-cholesterol and total triglycerides arenot significantly affected by soy cotyledon fibres. In the presentinvention, soybean fibres, in particular from the cotyledon of soybeans,are believed to provide a synergistic effect in combination withisolated soy protein so as to lower lipid concentration in subjects bothhaving normal and elevated concentrations of total cholesterol and totaltriglycerides. The amount of soybean fibres shall be a maximum of 50weight % of the isolated soy protein, and preferred amounts are between25 and 33 weight %. The amount of soybean fibres is preferably at least5 weight % of the total weight of the nutritional composition on a drybasis. The preferred daily dosage, when the nutritional composition ofthe invention is used as a total diet, is 20-30 g soybean fibres. Aparticularly, preferred soy cotyledon fiber product is manufactured byProtein Technologies International under the trademark FIBRIM®, andamong the various soy fibres produced under the FIBRIM® brand, FIBRIM®1020 is preferred according to the present invention because it has aparticularly good mouthfeel and dispersibility for dry blended beverageapplications

As mentioned above, isolated soy protein is preferably the main- or solesource of protein, but other proteins may be present. The proteincontent should provide at least 15% of the total energy content of thecomposition. More preferred, the protein provides at least 20%,preferably at least 25% and more preferred at least 30% of the totalenergy content of the composition. In terms of weight, it is preferredthat the isolated soy protein amounts to no less than 50 weighty %,preferably no less than 75 weight %, and more preferred no less than 90weight %, of the total protein content of the composition. Such weightproportions of protein are much higher than in the diets studied byPotter et al. (loc cit) and Bakhit et al. (loc sit).

A composition according to the present invention may optionally comprisea carbohydrate source, a fat source, flavouring agents, vitamins,minerals, electrolytes, trace elements and other conventional additives.If any of these optional ingredients are not present in the compositionof the invention, they should normally be supplied as a supplement tothe nutritional composition of the invention, so that an adequate supplyof all essential nutritional ingredients is ensured. If the compositionof the invention is intended to supply a substantial part of the foodintake of a subject, the optional ingredients are preferably present, sothat separate intake thereof can be avoided. This is of particularimportance for overweight or obese subjects on a weight reductiontreatment, by which it is important that all essential nutritionalingredients are supplied in recommended amounts.

When a carbohydrate source is present in the composition, it ispreferably present in an amount of less than 50 weight % of thecomposition. Preferably the amount of carbohydrate amounts to at least20 weight %, more preferred at least 25 weight %, and most preferred atleast 30 weight %, of the composition.

The preferred carbohydrates for use in the invention are glucose,fructose and for maltodextrine. Skimmed milk and cocoa are otherpossible carbohydrate sources.

When a fat source is present in the composition of the invention, it isusually present in an amount from 3 to 50 weight %, preferably 4 to 40weight %, more preferably from 4 to 12 weight %, and most preferablyfrom 5 to 10 weight %. of the composition. The fat source willpreferably comprise polyunsaturated fatty acids and monounsaturatedfatty acids as well as saturated fatty acids. The amount ofpolyunsaturated fatty acids and monounsaturated fatty acids, includingthe essential fatty acids, may range from 35 to 50, preferably 38 to 44,weight % of the total amount of the fat source. The essential fattyacids are also called omega-6 and omega-3 fatty acids and includelinolic acid and linolenic acid. The amount of saturated fatty acids maybe from 20 to 30 weight %, preferably 22 to 26 weight %, of the totalamount of fat.

Normally, the nutritional composition of the invention will alsocomprise one or more flavouring agents such as cocoa, vanilla, lime,strawberry or soup flavours, such as mushroom, tomato or bouillon.

Vitamins and minerals will be added to the composition in accordancewith the limits laid down by health authorities. Preferably, thecomposition of the invention will comprise all recommended vitamins andminerals. The vitamins will typically include A, B1, B2, B12, folicacid, niacin, panthotenic acid, biotin, C, D, E and K. The minerals willtypically include iron, zink,iodine, cobber, manganese, chromium andselenium. Electrolytes, such as sodium, potassium and chlorides, traceelements and other conventional additives are also added in recommendedamounts.

The composition of the invention may take any form which is suitable forhuman consumption. In a preferred embodiment, the composition is apowdery mixture which is suspendable, dispersible or emulsifiable in awater-containing liquid such as water, coffee, tea or fruit juice. Forsuch purpose, the composition is preferably packed in a package intendedfor covering the total nutrition requirement for a defined period oftime, such as three days or a week, whereby the composition will bedivided into suitable sub-units of a daily dose, preferably four to fivesub-units for women and four to six sub-units for men per daily dosage,which are packed separately before being packed into the package, or thepackage will be provided with means for a portioning of such sub-units.

In another preferred embodiment, the composition of the invention is aliquid nutritional preparation in a water-containing liquid, in whichthe solid ingredients are suspended, dispersed or emulgated in an amountof 10 to 25 weight , When the liquid nutritional preparation is intendedfor drinking, it will usually comprise a flavouring agent as discussedabove. However, the liquid nutritional preparation may also be used forintravenous administration or for probe administration.

In a further embodiment, the nutritional composition of the inventionmay be in the form of a solid composition such as a nutritional bar,fruit bar, cookie, cake, bread or muffin.

In another aspect, the invention relates to the use of a compositionaccording to the invention as partial or total diet for overweight or.obese subjects. Overweight or obese persons often have an increasedserum cholesterol level and an increased triglyceride level, and thecomposition of the invention will have the effect of lowering thesevariables. Very surprisingly, the composition of the invention also hasa substantial lowering effect on total serum cholesterol level and totaltriglyceride level in persons having a normal lipid profile. For thepurpose of the present invention, subjects having an initial total serumcholesterol level of 5.7 mmol/l or below are considered to have a normalor hypocholesterolemic level, whereas subjects having a total serumcholesterol level above 5.7 mmol/l are considered to behypercholesterolemic. It is believed that a significant lipidloweringeffect on subjects having a normal serum cholesterol level has notpreviously been observed as a result of treatment with a composition onbasis of soybean ingredients comprising isolated soy protein and soybeanfibres such as soy cotyledon fibres. Therefore, in a further aspect, theinvention provides for the use of a composition according to theinvention as a medicament for lowering the blood cholesterol level andthe triglyceride level, and for increasing the HDL/LDL-cholesterol ratioin serum. The medical use of the composition according to the inventionis not limited to overweight or obese subjects, but may also be used fornormal weight subjects having increased serum cholesterol level. Asmentioned previously, the composition according to the invention alsohas a lowering effect upon the increase in uric acid concentrationnormally found in weight reduction treatments where protein may bedegradated from the fat-free body mass, e.g. the musculature. Therefore,a composition according to the invention provides for increased safetyif used as a total meal replacement.

A composition according to the invention may also be used as a partialmeal replacement for lowering cholesterol in hypercholesterolemicpatients. For example, one to three daily meals of ordinary food can bereplaced by a composition according to the present invention. Hereby,significant cholesterol and triglyceride reductions can be obtained, aswell as improvement of HDL/LDL cholesterol ratio.

For use in a weight loss treatment, the daily dose of the composition ofthe invention may comprise an energy content from 400 to 800, inparticular from 450 to 800 kcal/day, which is considered to be a verylow calorie diet (VLCD), or it may comprise from 800 to 1200 kcal/day,which is considered to be a low-calorie diet (LCD). In the medicalaspect of the invention, the energy content may correspond to the dailyenergy requirement of a normal person, or the composition can be used asan emergency ration in isolated areas, in which case the energy contentmay correspond to 2000-2500 kcal/day.

The composition of the present invention will also be useful in ananti-smoking programmed to avoid weight gain after smoking cessation.For such a purpose, a composition according to the present invention maybe used in combination with a nicotine substitution such as nicotinechewing gum or a corresponding nicotine patch. Since use of acomposition according to the present invention may counteract a weightgain, smokers may hereby become more motivated for quitting tobacco witha possibly higher success rate in smoking cessation

The invention will be further illustrated in the following, non-limitingexamples.

EXAMPLE 1

The following ingredients were mixed:

Isolated soy protein 60 g Fat 8 g Carbohydrate 50 g Soy fiber 20 gVitamins, minerals, electrolytes and 5 g trace elements, approximately

The mixture was suspended in approximately 1000 ml water to provide adrink comprising about 530 kcal, corresponding to the daily dosage for aVLCD preparation.

EXAMPLE 2

The following ingredients were mixed:

Isolated soy protein 75 g Fat 22 g Carbohydrate 100 g Soy fiber 20 gVitamins, minerals, electrolytes and 5 g trace elements, approximately

The mixture was suspended in approximately 1000 ml water to provide adrink comprising about 880 kcal, corresponding to the daily dosage for aLCD preparation.

EXAMPLE 3

The products of examples 1 and 2 were investigated in a clinical trialat Karolinska Hospital, Stockholm, Sweden.

The number of patients needed in each treatment group was calculated to27 in order to detect a true treatment difference of 4 kg between thetreatment groups VLCD/530 and LCD/880, using an estimate of the standarddeviation of 12, using a significance level of 5%/3=1.7% and a power of80% .

The patients were selected according to the following inclusioncriteria:

Moderate to severe overweight persons with body mass index (BMI) <30kg/rM²

both sexes

age between 20 and 65

a self-reported, stable body weight within the last two months.

TABLE 1 Description of age (years). Treatment N Mean SD Min Max 530kcal/day 32 40.84 12.54 22 65 880 kcal/day 31 39.39 10.15 24 65

TABLE 2 Description of sex distribution. 530 880 Sex kcal/day kcal/dayMale 10 10 Female 22 21

TABLE 2 Description of sex distribution. 530 880 Sex kcal/day kcal/dayMale 10 10 Female 22 21

WEIGHT

The weight was recorded at every visit for the subjects in all threegroups. The weight is described below.

TABLE 4 Description of weight (kg). 880 kcal/ 530 kcal/day day Week NMean SD Min Max N Mean SD Min Max 0 32 113.8 18.0 81.0 158.9 31 113.818.7 85.6 157.1 6 28 99.0 15.5 72.7 127.9 29 103.1 15.6 80.1 136.7

TABLE 4 Description of weight (kg). 880 kcal/ 530 kcal/day day Week NMean SD Min Max N Mean SD Min Max 0 32 113.8 18.0 81.0 158.9 31 113.818.7 85.6 157.1 6 28 99.0 15.5 72.7 127.9 29 103.1 15.6 80.1 136.7

From the above table, it can be calculated that VLCD/530 provided acholesterol reduction of 25% in six weeks, and LCD/880 provided acholesterol reduction of 26.8% in six weeks. In VLCD/530 the daily fatintake. was 8 g, and in LCD/880 it was 22 g. The initial cholesterollevel of 5.6 mmol/ in both treatment groups corresponds to a normalcholesterol level, and as can be noted there is a significant reductionof cholesterol after six weeks, which is higher when the intake of fat,carbohydrate and soy protein is increased.

TABLE 6 Description of triglycerides (mmol/l) 880 kcal/ 530 kcal/day dayWeek N Mean SD Min Max N Mean SD Min Max 0 32 2.0 1.1 0.8 5.9 31 1.8 1.00.7 4.5 6 28 1.4 0.5 0.7 3.1 27 1.0 0.3 0.8 2.3

From the values in the table it can be calculated that the triglycerideconcentration was lowered by 30% in the group receiving the LCD/530, and44,5% in the group receiving LCD 880. Again it can-be seen that thereduction of triglyceride concentration was highest in the groupreceiving most fat, carbohydrate and isolated soy protein.

TABLE 7 Description of uric acid (μmol/l). 880 kcal/ 530 kcal/day dayWeek N Mean SD Min Max N Mean SD Min Max 0 32 338.3 66.8 182 466 30316.2 78.8 109 457 6 28 413.1 118.3 148 803 29 364.3 111.4 73 539

From the table it can be calculated that uric acid concentrationincreased by 35 22.1% in the group receiving the LCD/530 and by 15.2% inthe group receiving the LCD/880. In a comparative study with a VLCD/420product prepared according to EP-0 425 423 B1 and which containedsoybean concentrate with fibres, the uric acid concentration increasedby 27.9% in the same six week period.

EXAMPLE 4 (COMPARISON)

A nutrition powder prepared according to EP-0 425 423 B1 isconcentrically available under the trademark NUTRILETT® VLCD 420. Thiscomposition provides 420 kcal per day and comprises 61.5 g protein as acombination of soy protein concentrate and skimmed milk powder, 6.0 gfat, including 2.0 g poly-unsaturated fat, 30.5 g carbohydrates and 17.5g fibres derived from soy protein concentrate. The product is suppliedwith a fish oil capsule containing essential omega-3 fatty acids and atablet containing Nordic Recommended Daily Allowances (RDA) of thevitamins, minerals and trace elements which do not occur sufficiently inthe nutrition powder. VLCD 420 was compared with the products of Example1 (VLCD 530) and Example 2 (LCD 880) and the results are shown in TablesI and II below.

TABLE I DESCRIPTION OF CHOLESTEROL VALUE AT WEEK 0 CHOLESTEROL RECEIVEDVALUE AT CHOLESTEROL VALUE AT WEEK 0 TREATMENT STUDY START SEX N MEANSTD MIN MAX VLCO 420 <5 mmol/l MALE 1 4.80 4.80 4.80 KCAL FEMALE 4 4.500.38 4.00 4.80 >5 mmol/l MALE 9 5.86 0.73 5.00 6.80 FEMALE 15 5.83 0.725.00 7.00 VLCD 530 <5 mmol/l MALE 2 4.85 0.21 4.50 4.80 KCAL, 6W FEMALE5 4.18 0.37 3.60 4.60 >5 mmol/l MALE 8 6.01 1.02 5.00 8.00 FEMALE 175.89 0.62 5.00 7.50 LCD 880 KCAL <5 mmol/l MALE 2 4.60 0.28 4.40 4.80FEMALE 8 4.40 0.47 3.50 4.90 >5 mmol/l MALE 8 6.25 0.68 5.30 7.20 FEMALE13 5.97 0.66 5.20 7.40

TABLE II DESCRIPTION OF CHOLESTEROL REDUCTION FROM WEEK 0 TO WEEK 6CHOLESTEROL RECEIVED VALUE AT CHANGE IN CHOLESTEROL W 0-6 TREATMENTSTUDY START SEX N MEAN STD MIN MAX VLCO 420 <5 mmol/l MALE 1 1.40 1.401.40 KCAL FEMALE 4 0.65 0.67 0.30 1.20 >5 mmol/l MALE 9 1.50 0.92 0.302.80 FEMALE 14 1.13 0.56 0.10 2.00 VLCD 530 <5 mmol/l MALE 2 1.05 0.490.70 1.40 KCAL, 6W FEMALE 3 1.00 0.25 0.70 1.20 >5 mmol/l MALE 8 1.730.96 0.40 3.40 FEMALE 15 1.51 0.73 −0.10 2.40 LCD 880 KCAL <5 mmol/lMALE 2 0.95 0.35 0.70 1.20 FEMALE 7 0.83 0.83 −0.40 1.80 >5 mmol/l MALE8 2.05 0.73 1.00 3.20 FEMALE 12 1.34 0.82 −0.20 3.20

From the results of table I and table II it can be concluded that theVLCID 530 lowers cholesterol by 25% and LCD 880 lowers cholesterol by27% during six weeks treatment. The LCD 880 is thereby more than 20%more effective regarding cholesterol reduction than the previous VLCD420 product even though the latter only provides 6 g fat per day incontrast to 22 g fat per clay for the composition of the presentinvention. Furthermore it can be seen that patients having a higherinitial cholesterol value obtains a higher cholesterol lowering effect.For example the cholesterol lowering for men treated six weeks with theLCD 880, and having an initial cholesterol value of 6.25, was 32.8%.

EXAMPLE 5 (COMPARISON)

In another study NUTRILETT® VLCD 420 with the composition stated inExample 4 was given to a population of 152 females and 101 males, aged15-72 years (median 41.6). Their body weight ranged from 70-177 kg(median 99.7) and body mass index (BME) from 25-51 kg/m2 (median 33.2).The patients were mildly hypercholesterolemic having an average totalcholesterol of 6,0 mmol/l, and it was found that the mean totalcholesterol level was lowered to 4.8 mmol/l after eight weeks oftreatment with the preparation. In the same eight weeks' period theconcentration of triglycerides was lowered from 3.1 mmol/l to 1.2mmol/l.

The reduction in average total cholesterol from 6.0 mmol/l to 4.8 mmol/lin mildly hypercholesterolemic patients corresponds to 20%.

EXAMPLE 6

A hypercholesterolemic patient was treated with Zocor® (one of thestatins) whereby the serum cholesterol level was reduced to 6 mmol/l.Subsequently, the patient replaced his evening meal during one month bythe LCD 880 preparation according to the present invention, whereby thecholesterol level was further reduced to 5.3 mmol/I (=12% reduction) andthe triglyceride level was reduced from 2.66 to 2.15 mmol/l (=19%reduction). This shows that a further reduction in cholesterol andtriglycerides may be obtained by a composition according to the presentinvention for a patient who has already been treated with a cholesterollowering medicament.

EXAMPLE 7

A patient reduced the cholesterol level from 10 mmol/l to 8.3 mmol/l bymeans of a medical diet with a reduced fat and calorie intake. Byreplacing two daily meals with the LCD 880 according to the presentinvention, the cholesterol level was further reduced to 6.5 mmol/lduring a three months period. This is a 22% reduction in comparison withthe cholesterol level which was possible with the medically recommendeddiet.

What is claimed is:
 1. A composition comprising: (a) isolated soyprotein; and (b) soybean fibers; the weight of (a) and the weight of (b)being in a predetermined weight ratio; wherein the composition has atotal protein content and a total energy content such that the totalprotein content provides at least 15% of the total energy content, andwhere (I) the weight ratio of (a) to (b) is at least 2, and the isolatedsoy protein is present in an amount of at least 75 weight percent of thetotal protein content of the composition, or (II) the weight ratio of(a) to (b) is at least 3, and the isolated soy protein is present in anamount of at least 50 weight percent of the total protein content of thecomposition, or (III) the weight ratio of (a) to (b) is in the range of3 to
 4. 2. The composition of claim 1 where clause (I) applies.
 3. Thecomposition of claim 1 where clause (II) applies.
 4. The composition ofclaim 1 where clause (III) applies.
 5. The composition of claim 1 inwhich the weight ratio of (a) to (b) is at least
 3. 6. The compositionaccording to claim 2 wherein isolated soy protein is present in anamount of at least 50 weight percent of the total protein content of thecomposition.
 7. The composition according to claim 2 wherein isolatedsoy protein is present in an amount of at least 75 weight percent of thetotal protein content of the composition.
 8. The composition accordingto claim 1 wherein isolated soy protein is present in an amount of atleast 90 weight percent of the total protein content of the composition.9. The composition according to claim 1 wherein substantially all of theprotein is isolated soy protein.
 10. A method of protecting a subjectfrom an undsirable condition inhibitable by a composition comprising (a)isolated soy protein, and (b) soybean fibers; said method comprisingadministering to the subject an effective amount of said composition;the weight of (a) and the weight of (b) being in a predetermined weightratio; wherein the composition has a total protein content and a totalenergy content such that the total protein content provides at least 15%of the total energy content; where (I) the weight ratio (a) to (b) is atleast 2, and the isolated soy protein is present in an amount of atleast 75 weight percent of the total protein content of the composition,or (II) the weight ratio of (a) to (b) is at least 3; and with theproviso that, if the subject is a person afflicted with cancer, saidundesirable condition is not a nutritional need attributable tochemotherapy or radiation therapy for said cancer.
 11. A method ofprotecting a subject from an undesirable condition inhibitable by acomposition comprising (a) isolated soy protein, and (b) soybean fibers;said method comprising administering to the subject an effective amountof said composition; the weight of (a) and the weight of (b) being in apredetermined weight ratio; wherein the composition has a total proteincontent and a total energy content such that the total protein contentprovides at least 15% of the total energy content; where (I) (a) and (b)are in a weight ratio of at least 2, and the isolated soy protein ispresent in an amount of at least 75 weight percent of the total proteincontent of the composition, or (II) the weight ratio of (a) to (b) is atleast 3; and where said subject is overweight or obese, is sufferingfrom increased levels of serum triglycerides or serum cholesterol, or isa smoker.
 12. A method of protecting a subject from an undesirablecondition inhibitable by the composition of claim 1, said methodcomprising administering to the subject an effective amount of saidcomposition, with the proviso that, if the subject is a person afflictedwith cancer, said undesirable condition is not a nutritional needattributable to chemotherapy or radiation therapy for said cancer.
 13. Amethod of protecting a subject from an undesirable condition inhibitableby the composition of claim 1, said method comprising administering tothe subject an effective amount of said composition, where said subjectis overweight or obese, is suffering from increased levels of serumtriglycerides or serum cholesterol, or is a smoker.